1. Field of the Invention
This invention relates to a product containing an extract from Zanthoxylum avicennae (Lam.) DC. and a preparation process thereof. This invention also relates to a pharmaceutical composition which comprises the product containing the extract from Zanthoxylum avicennae (Lam.) DC.
2. Description of the Related Art
Cancer is one of the leading causes of human death nowadays. Particularly, liver cancer is one of the most common types of cancer. The mechanism of carcinogenesis has not been completely understood. However, carcinogenesis can be attributed to the following reason. When genetic abnormalities are induced by exogenous or endogenous factors with respect to cells, signal transduction in the cells may become abnormal, thereby further giving rise to uncontrolled cell division. Cancer cells are accordingly formed. Furthermore, the cancer cells may continuously proliferate and may metastasize to other portions of the body through the lymphatic system or the vascular system.
Generally speaking, deactivation of the apoptosis signal transduction pathway (e.g., the death receptor-dependent apoptosis signal transduction pathway and the mitochondria-dependent apoptosis signal transduction pathway) and/or activation of the cell survival signal transduction pathway may result in proliferation of cancer cells. In addition, activation of the urokinase plasminogen activator signal transduction pathway, the mitogen-activated protein kinase (MAPK) signal transduction pathway, or the β-catenin signal transduction pathway may lead to metastasis of cancer cells. Therefore, in recent years, research in inhibiting proliferation and metastasis of cancer cells, and inducing apoptosis of cancer cells, by virtue of deactivation and/or activation of the aforesaid signal transduction pathways has become important for developing an anticancer drug.
Effects of the conventional anticancer drugs on cancer are unsatisfactory basically due to individual differences of patients, severe side effects thereof, and drug resistance of cancer cells. In view of the foregoing, some researchers have attempted to find active components, which can be used in cancer treatment, from traditional Chinese medicine (TCM).
Zanthoxylum avicennae (Lam.) DC. (trivial name: avicennia pricklyash; YING BU BO in pinyin) is a perennial evergreen shrub or an arbor which belongs to Rutaceae, and the trunk and the branch thereof have reddish brown prickles. Zanthoxylum avicennae (Lam.) DC. can be found in Taiwan, China, Vietnam, Laos, Cambodia, etc. It is reported that each portion of Zanthoxylum avicennae (Lam.) DC. (e.g., a root, a stem, a leaf, fruit, etc.) is wholesome or has a therapeutic effect (Nanjing University of Chinese Medicine, Dictionary of Chinese Materia Medica, Shanghai Scientific and Technical Publisher, 2006, 2nd edition, Volume 2, pages 3824-3825).
It is recorded that: the fruit of Zanthoxylum avicennae (Lam.) DC. has therapeutic effects on stomachache and abdominal pain; the leaf of Zanthoxylum avicennae (Lam.) DC. has therapeutic effects on bone-setters injury, strain of lumbar muscles, mastadenitis, and swollen boil; and the root of Zanthoxylum avicennae (Lam.) DC. has therapeutic effects on icterohepatitis, jaundice edema, hepatitis B, hepatocirrhosis, edema due to nephritis, bone-setters injury, rheumatoid arthritis, strain of lumbar muscles, leucorrhea, common cold, sore throat, cough, malaria, colitis, and stomatitis (Bian Xie Zu, Meaning Whole China Herb Conglomeration Edition, Journal of People's Public Health, 1975, 1st edition, Volume 1, pages 928; Lan-Chang Zhang, Dictionary of Chinese Herbs, Chao Ren Press, 1981, Volume 5, pages 5513-5514; Nanjing University of Chinese Medicine, Dictionary of Chinese Materia Medica, Shanghai Scientific and Technical Publisher, 2006, 2nd edition, Volume 2, pages 3824-3825).
The following experiment was conducted by T. T. Thuy et al. [T. T. Thuy et al. (1999), Phytochemistry, 50:903-907]. The leaf of Zanthoxylum avicennae (Lam.) DC. was subjected to an extraction treatment using 95% MeOH at room temperature, and MeOH was removed by virtue of distillation under vacuum. The resultant aqueous solution was extracted with n-hexane, followed by EtOAc and n-BuOH. n-BuOH was removed under vacuum, and the residue was subsequently subjected to partitioning using CHCl3 and H2O. The CHCl3 layer was collected, followed by removing CHCl3 under vacuum so as to obtain an extract from the leaf of Zanthoxylum avicennae (Lam.) DC. The extract from the leaf of Zanthoxylum avicennae (Lam.) DC. was further subjected to isolation and purification, thereby acquiring three novel alkaloids, i.e., (−)-culantraramine N-oxide, (−)-culantraraminol N-oxide, and avicennamine.
J. J. Chen et al. reported that: in a previous study, an extract from the stem wood of Zanthoxylum avicennae (Lam.) DC. was prepared by the process including subjecting the stem wood of Zanthoxylum avicennae (Lam.) DC. to an extraction treatment with cold MeOH, concentrating the resultant product under reduced pressure, conducting a partitioning treatment with EtOAc and H2O, and collecting the thus formed EtOAc-soluble fraction [J. J. Chen et al. (2008), Journal of Natural Products, 71:212-217]. The extract from the stem wood of Zanthoxylum avicennae (Lam.) DC. was proven to be able to suppress FMLP/CB (formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochal-asin B)-induced superoxide anion generation and elastase release, thereby having anti-inflammatory activity. Accordingly, J. J. Chen et al. further isolated and purified the extract from the stem wood of Zanthoxylum avicennae (Lam.) DC. such that eight new compounds, including four neolignans, a coumarinolignan, two lignan derivatives, and a chromene, were obtained. Furthermore, J. J. Chen et al. evaluated anti-inflammatory effects of the eight compounds on FMLP/CB-induced superoxide anion generation and elastase release.
In order to cure cancer, the applicants have endeavored to investigate activities of Zanthoxylum avicennae (Lam.) DC., and have found that a product containing an extract from Zanthoxylum avicennae (Lam.) DC. is able to inhibit proliferation and metastasis of tumor/cancer cells, and to induce apoptosis of tumor/cancer cells. Furthermore, the product containing the exatract from Zanthoxylum avicennae (Lam.) DC. is also capable of suppressing tumor cell proliferation in vivo and increasing tumor cell apoptosis in vivo. Consequently, the product containing the extract from Zanthoxylum avicennae (Lam.) DC. is expected to be useful in a cancer treatment.